In recent years, tetrahydroquinolines are widely used as pharmaceuticals, etc., and a variety of methods for producing them have been studied.
Production methods of tetrahydroquinolines via amino acid derivatives as intermediates have been disclosed (patent references 1 and 2, etc).
The patent references 1 and 2 disclose production methods of tetrahydroquinolines in which secondary amines obtained by the reactions of primary amines with aryl halogenides are used as the starting material. However, those methods require that the reaction conditions are selected so as not to bring about racemization in the process of introducing an alkyl or aryl group onto the amino group of optically active primary amines such as amino acids.
The non-patent reference 1 discloses a method for producing optically active amino acids in which the amino group is a secondary one by way of an asymmetric nucleophilic addition to the imines. However, for obtaining the desired amines, it is indispensable to use an excess amount of flammable diethylzinc, which has drawbacks in the workability, etc. of the reaction.
The non-patent reference 2 discloses a method for producing β-amino acid derivatives, in which enamines obtained by substituting the remaining hydrogen atom of a secondary amino group with an acetyl group, to an asymmetric hydrogenation. However, the method of the non-patent reference 2 has a drawback of requiring protection of the secondary amino group with a protecting group such as an acetyl group, etc., before subjecting the enamines to asymmetric hydrogenation, thus making two extra processes of introduction and removal of the protecting group indispensable.
Patent reference 1: WO02/088069
Patent reference 2: WO02/088085
Non-patent reference 1: Chemistry Letters, 254-255 (2001).
Non-patent reference 2: Tetrahedron Asymmetry, Vol. 2, No. 7, 543-554 (1991).